Anthelmintic efficacy and dose determination of Albizia anthelmintica against gastrointestinal nematodes in naturally infected Ugandan sheep

Weight loss, stunted growth, and death caused by gastrointestinal parasites are major constraints to livestock productivity, especially in tropical and developing countries where regular use, and misuse, of anthelmintics has led to nematode resistance. Albizia anthelmintica Brong. (Fabaceae) is traditionally employed throughout East Africa to treat helminth parasitosis in livestock. Reported efficacy has varied from 90% against mixed nematodes to just 19% against Haemonchus contortus alone. The objective of this study was to assess the anthelmintic effect of A. anthelmintica against naturally occurring infections of mixed gastrointestinal parasites, and to establish an effective treatment dose, in sheep under pastoral field conditions of northern Uganda. A. anthelmintica bark was collected and prepared according to local custom and packed into gel capsules. Fifty-five young female local mixed-breed lambs were randomly assigned to six groups, including a positive control group that received levamisole (synthetic anthelmintic) and a negative control group that received no treatment. Following the World Association for the Advancement of Veterinary Parasitology (WAAVP) dose determination guidelines, the other four groups were treated with varying doses of A. anthelmintica. Statistical analyses (using generalized linear models) were performed to assess treatment effect. There was a significant treatment (group) effect on parasite egg/oocyte counts per gram (EPG) for nematodes, but not for coccidia. The most effective dose against nematodes (0.8g, 58.7mg/kg) closely approximates what is usually given by traditional healers, 0.9g/adult sheep. It provided major and significant reduction in EPG as compared to the negative control. Anthelmintic efficacy was estimated using percent faecal egg count reduction (FECR). Other than the positive control, animals in the standard dose group showed the greatest decline in shedding of nematode eggs, with an FECR of 78%. This study indicates that A. anthelmintica holds potential as part of an integrated management plan for the control of helminths in developing countries.     

Global perspectives on nematode parasite control in ruminant livestock: the need to adopt alternatives to chemotherapy,with emphasis on biological control

Effective, sustainable control of nematode parasites of grazing livestock is becoming evermore challenging and difficult. This is largely due to two contrasting issues. One is the rapid escalation of resistance to anthelmintic drugs, which is arguably the greatest problem now facing the small ruminant industries worldwide. Secondly, there is the increasing trend towards organic farming, in which there is prohibition of the prophylactic use of all chemical compounds. Livestock producers urgently need non-chemotherapeutic alternatives in parasite control. Researchers have responded to this challenge and a variety of quite different approaches have been the subject of intense investigation in many countries for several decades now. These vary in relation to their stage of development for on-farm use, their utility, and their applicability across the spectrum of grazing livestock enterprises throughout the world. One relatively recent innovation is the biological control approach to nematode parasites. This has now reached the stage of commercialization. This review focuses on these issues and provides an overview of the possible ways in which the biological control of nematode parasites could be employed in grazing ruminant livestock systems worldwide.     

The anthelmintic efficacy of the plant, Albizia anthelmintica, against the nematode parasites Haemonchus contortus of sheep and Heligmosomoides polygyrus of mice

Albizia anthelmintica Brong., belongs to the plant family Mimosaceae. The plant is widely used in East Africa by poor smallholder farmers and pastoralists to treat their livestock against internal parasites. The anthelmintic effects of water extracts from the bark of A. anthelmintica, obtained from three different geographic areas in Kenya and using different methods of preparation, were tested at different doses in sheep and mice infected with the nematode parasites Haemonchus contortus and Heligmosomoides polygyrus, respectively. Lambs were infected with 3000 infective larvae of H. contortus and treated with the plant preparations 28 days later, while mice were infected with 200 infective larvae of H. polygyrus and treated 18 days later. Proximate analysis established high levels of crude proteins in A. anthelmintica bark. Two sheep out of the 45 treated with the plant preparations suffered from transient bloat, which was relieved by dosing with a surfactant. Significant reductions in faecal egg counts were observed in lambs treated with A. anthelmintica in two of the three experiments undertaken, but the efficacy levels achieved were well below the 70% reduction required. Similar values of packed red cell volume and live weight gain were observed for treated and control lambs. There was no overall significant effect of treatment with A. anthelmintica on faecal egg and total worm counts in mice. A dose rate of 1000 mg/kg bodyweight of A. anthelmintica preparation resulted in death of all mice. The results show that A. anthelmintica at the doses and preparations used is not efficacious against H. contortus in sheep or against H. polygyrus in mice.     

Use of plants in novel approaches for control of gastrointestinal helminths in livestock with emphasis on small ruminants

Helminth infections are a major cause for reduced productivity in livestock, particularly those owned by the poor worldwide. Phytomedicine has been used for eons by farmers and traditional healers to treat parasitism and improve performance of livestock, and many modern commercial medicines are derived from plants. However, scientific evidence on the anti-parasitic efficacy of most plant products is limited, regardless of their wide ethnoveterinary usage. Scientific validation of the anti-parasitic effects and possible side-effects of plant products in ruminants is necessary prior to their adoption as a novel method for parasite control. A variety of methods has been explored to validate the anthelmintic properties of such plant remedies, both in vivo and in vitro. In vitro assays are useful as pre-screens of activity and are mainly performed with the free-living rather than parasitic stages of nematodes. Concentrations of potentially active substances used in vitro do not always correspond to in vivo bioavailability. Therefore, in vitro assays should always be accompanied by in vivo studies when used to validate the anthelmintic properties of plant remedies. In vivo controlled studies have shown that plant remedies have in most instances resulted in reductions in the level of parasitism much lower than those observed with anthelmintic drugs. Whether it is necessary or not to achieve very high efficacy in order for plant remedies to have a role in the control of parasitism depends on the determination of biologically important levels of reduction of parasitism and it will be required prior to the wide-scale use of plant products for parasite control. Similarly, standardisation of validation studies in reference to the numbers of animals required for in vivo studies to measure direct anthelmintic effects of a plant needs to be established. Although in many cases the active compounds in the herbal remedies have not been fully identified, plant enzymes, such as cysteine proteinases, or secondary metabolites, such as alkaloids, glycosides and tannins have shown dose-dependent anti-parasitic properties. However, as some of the active compounds may also have anti-nutritional effects, such as reduced food intake and performance, it is essential to validate the anti-parasitic effects of plant products in relation to their potential anti-nutritional and other side effects. A concerted effort on isolation, development, and validation of the effects of these herbal remedies will have to be undertaken before their wider acceptance.     

Infection with parasitic nematodes confounds vaccination efficacy

T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a specific example of the need for further work in this area, and for controlled field studies to assess the impact of other similar scenarios.     

Anthelmintic resistance of nematode parasites of small ruminants in eastern Ethiopia: exploitation of refugia to restore anthelmintic efficacy

Faecal egg count reduction tests (FECRT) were conducted in May 2003 to determine the efficacy of anthelmintics used for treatment against nematode parasites in separately managed sheep and goat flocks at Alemaya University in eastern Ethiopia. These tests revealed high levels of anthelmintic resistance to albendazole, tetramisole, the combination of these two drugs, and to ivermectin in the goat flock (predominantly infected by Haemonchus contortus and Trichostrongylus spp.), whereas all drugs were highly efficacious in the sheep flock. A second FECRT confirmed these observations. Following this, a new management system was implemented on the goat flock for a period of 9 months (January-September 2004) in an attempt to restore the anthelmintic efficacy. This involved a combination of measures: eliminating the existing parasite infections in the goats, exclusion from the traditional goat pastures, and introducing communal grazing of the goats with the university sheep flock and livestock owned by neighbouring small-holder farmers. A second series of FECRTs (Tests 3 and 4) conducted 7 months after this change in management, showed high levels of efficacy to all three drugs (albendazole, tetramisole and ivermectin) in the goat flock. This is the first field study to demonstrate that anthelmintic efficacy in the control of nematode parasites of small ruminants can be restored by exploiting refugia.     

Ovine helminthosis, a major health constraint to productivity of sheep in Ethiopia

Small ruminants represent an important component of the Ethiopian livestock production system, providing 12% of the value of livestock products consumed at the farm level and 48% of the cash income generated. Ethiopia is second in Africa and sixth in the world in terms of sheep population. The country has, however, benefited little from this enormous resource owing to a multitude of problems, disease being the most important. Disease alone accounts for mortalities of 30% in lambs and 20% in adults. Productivity losses attributable to helminth parasites are often substantial. A loss of US $ 81.8 million is reported annually due to helminth parasites. In a country confronted with challenges of an ever-rising human population and food shortage, such enormous losses caused by helminth parasites, 'the silent predators', are intolerable. Therefore, helminth control should receive special attention in poverty reduction strategies through improved productivity of livestock if the present and future challenges of food shortage are to be addressed. Productivity loss due to helminth infections can be substantially reduced through implementation of effective disease control strategies, which require an understanding of the epidemiology and ecology of parasites and parasitic infections under local conditions. This paper reviews extensive evidence demonstrating that helminthosis is a major constraint to productivity of sheep in Ethiopia. It also discusses epidemiology and ecology of major helminth parasites in the country and suggests strategies for improved control in various agro-ecological zones and production systems.     

Towards the implementation of the "basket of options" approach to helminth parasite control of livestock: emphasis on the tropics/subtropics

The virtual reliance on anthelmintic drugs alone to control internal parasites of livestock is inappropriate and ultimately unsustainable. In the tropics and subtropics, widespread and high levels of anthelmintic resistance, particularly in nematode parasites of small ruminants, is rife. But more to the point, many farmers in these regions of the world are resource poor and cannot afford, or are reluctant to purchase drugs that may also be of dubious quality. As it is with any intervention, the benefits must outweigh the costs. This is not only in terms of conventional parameters such as reduced mortality and increasing productivity (meat, milk, fibre and traction power) of livestock, but also within the broad framework of helminths of veterinary/human importance, the aim should be a positive impact on reducing the threat of helminth zoonoses. However, understanding the issues involved and education of the end-users (farmers) is of fundamental importance, before any internal parasite control program should be promoted. Within the above context, we provide examples of how the "basket of options" approach could be adopted for the control of three quite disparate helminth problems in the tropics and subtropics, viz.: strongyle nematode infections of donkeys, the Taenia solium cysticercosis/taeniosis problem of pig and man and Haemonchus contortus infections in small ruminants. The "best practice" approaches can be defined as those "basket of options" that are practical, affordable, available and appropriate, whether to the commercial producer, or to the resource-poor farmer. Constraints that may restrict applying such options are accessibility to, and affordability of, suitable remedies and above all, the availability of information needed to make informed decisions in this regard.     

Evaluation of anthelmintic properties of extracts from some plants used as livestock dewormers by pastoralist and smallholder farmers in Kenya against Heligmosomoides polygyrus infections in mice

Parasitic nematodes are among the most common and economically important infectious diseases of grazing livestock, especially in small ruminants in the tropics and subtropics in Kenya the control of gastrointestinal nematode infections in sheep and goats is usually made with synthetic anthelmintics but substantial levels of anthelmintic resistance have been recorded. A number of medicinal plants, that may provide possible alternatives, and are used by pastoralists and smallholder farmers in Kenya as deworming agents for their livestock and equines, namely Aframomum sanguineum, Dodonea angustifolia, Hildebrandtia sepalosa, Myrsine africana, Rapanea melanophloeos from Kenya, and Azadirachta indica from Kenya and Malaysia, together with the chemicals embelin and santonin that occur in some of these plants, were evaluated against Heligmosomoides polygyrus in mice. Commercial anthelmintics, namely ivermectin, pyrantel and piperazine, were also investigated, both to validate the mouse model system and to assess efficacy of these drugs against H. polygyrus. Pyrantel and ivermectin were highly effective in reducing the numbers of H. polygyrus worms as well as eggs in faeces of the mice, but piperazine had a lower activity. Application of santonin and M. africana significantly reduced the number of total worm counts (TWC) but not faecal egg counts (FEC). The use of embelin, R. melanophloeos and A. indica reduced FEC but not TWC. In all cases, however, reductions were well below the a priori level of 70% required for biological significance. A. sanguineum, D. angustifolia and H. sepalosa had no effect on either TWC or FEC. In conclusion, none of the plant preparations had any biologically significant anthelmintic effect in this monogastric host-parasite model system.     

Parasitic helminths of veterinary importance in cattle,sheep and goats on communal farms in the northeastern Free State,South Africa

The purpose of the study was to record and determine intensities, seasonal incidence and distribution of helminth parasites of veterinary importance that occur in cattle, sheep and goats in the northeastern Free State. The study was conducted at Harrismith and Kestell and in Qwa-Qwa from March 2000 to May 2001. Cattle of various breeds (including Bonsmara, Simmentaler and Friesian), Merino sheep and Angora goats were sampled. Faecal samples were analysed using the McMaster and Visser sieve techniques for egg counts and faecal cultures for 3rd-stage nematode larvae identification. Haemonchus and Oesophagostomum were the dominant nematode genera found to be infecting the animals. The socioeconomic status of the farmers in the study area was determined through a questionnaire survey aimed at recording their management strategies. It indicated that 81% of farmers take care of their livestock by feeding them with supplements. The low to moderate faecal egg counts from cattle showed that helminth infections in this region are still under control even though helminthosis seems to be a problem in small-stock, since EPG counts of more than > 1000 were found. Cattle farmers in this region are encouraged to continue with good animal husbandry practices that have ensured that helminth infections rates are kept low. Small-stock farmers are, however, encouraged to control helminth infections in their sheep and goats by anthelmintic treatment.     

First report of Lagochilascaris (Nematoda: Ascarididae) eggs in a public park in Southern Brazil

Public parks, especially in developing countries, are places where stray animals run free and may contaminate the environment with different species of parasites. In an evaluation of environmental sanitation of these sites, soil samples were collected monthly from public parks in the Pelotas city, Rio Grande do Sul State, Southern Brazil. Eggs of the nematode Lagochilascaris sp. were found in a public playground. This is the first report of identification of this nematode in Southern Brazil.     

The efficacy of monepantel against naturally acquired inhibited and developing fourth-stage larvae of Teladorsagia circumcincta in sheep in the United Kingdom

The inhibition of Teladorsagia and other nematode genera at the early fourth-stage is a biological process that allows the parasites to survive in their host in a dormant state when prevailing conditions may otherwise kill them or prevent their progeny from surviving in the external environment. A study was conducted in Scotland to evaluate the efficacy of monepantel, an amino-acetonitrile derivative, against natural infections of inhibited fourth-stage Teladorsagia spp. larvae. At necropsy it was determined that the untreated control sheep were additionally infected with developing fourth-stage Teladorsagia spp. larvae and this is the first published evidence on the efficacy of monepantel against natural infections of this parasite and stage. The study sheep, which had grazed on naturally contaminated pastures since birth, were transferred to indoor housing after a subset of animals was examined to confirm the presence of inhibited larvae within the study population prior to the experiment. After 14 days of housing, monepantel was orally administered at 2.5 mg/kg to half of the animals. The sheep were necropsied seven days later and their parasite burdens recovered for the determination of efficacy, which was 99.7% for the inhibited stages and 99.3% for the developing fourth-stages. In conclusion, monepantel dosed orally at 2.5 mg/kg is a highly effective treatment against naturally acquired infections of inhibited and developing fourth-stage larvae of Teladorsagia spp.     

Prospects for biological control of nematode parasites of ruminants

Control of nematode parasites in ruminants is directed almost exclusively at the parasitic stage in the host using conventional anthelmintic therapy. However, to complete their life cycle, parasites have to develop through a series of free-living stages on pasture. It is within this environment that there is a vast range of cohabiting micro-organisms, some of which are known to infect or prey on nematodes. These include bacteria, protozoa, viruses and fungi. To date, most interest has been focused on those organisms producing chemical toxins which have been developed as anthelmintics, e.g. Streptomyces/avermectins. Yet the potential of predacious and nematoxic fungi and bacteria for the biological control of nematode parasites of livestock remains largely untapped. These organisms may well offer a cheaper and more sustainable approach to reducing the impact of parasitism in livestock.     

Anthelmintic drug resistance in the UK

The term 'anthelmintic drug resistance' describes the heritable ability of some nematode parasites to survive treatment with anthelmintic drugs at the recommended therapeutic dose levels. Genes for resistance appear to be present in many of the important pathogenic nematodes of ruminants and horses. Under intensive management systems, where heavy reliance is placed on anthelmintic drugs for worm control, the selection of resistant genotypes may result in increased reports of the drugs failing to control the nematode populations against which they are aimed. Anthelmintic resistance has been reported from many parts of the world, and in some countries multiple drug-resistant strains have emerged. In the UK, recent investigations indicate an increasing level of resistance to benzimidazoles among nematodes of sheep and horses. The incidence, diagnosis, epidemiology and implications of anthelmintic resistance are discussed.     

Chemo-immunization of ruminants againstBabesia,Anaplasma, Theileria andCowdria species

Current approaches to the procedure and clinical use of chemoimmunization to control babesiosis, anaplasmosis, theileriosis and heartwater in ruminants are discussed. The procedures comprise artificial infection of susceptible animals with more or less virulent strains of the causative parasites and subsequent or simultaneous treatment with an appropriate drug to moderate the reactions to the parasites. It is proposed that chemo-immunization be routinely carried out in the tropics as a method of immunizing susceptible cattle against these haemotropic infections before exposure to natural infection in the field. The method is particularly suitable for introduction of susceptible cattle into an enzootic area alongside an adequate tick control programme.     

Parasitic nematodes - from genomes to control

The diseases caused by parasitic nematodes in domestic and companion animals are major factors that decrease production and quality of the agricultural products. Methods available for the control of the parasitic nematode infections are mainly based on chemical treatment, non-chemical management practices, immune modulation and biological control. However, even with integrated pest management that frequently combines these approaches, the effective and long-lasting control strategies are hampered by the persistent exposure of host animals to environmental stages of parasites, the incomplete protective response of the host and acquisition of anthelmintic resistance by an increasing number of parasitic nematodes. Therefore, the challenges to improve control of parasitic nematode infections are multi-fold and no single category of information will meet them all. However, new information, such as nematode genomics, functional genomics and proteomics, can strengthen basic and applied biological research aimed to develop improvements. In this review we will, summarize existing control strategies of nematode infections and discuss ongoing developments in nematode genomics. Genomics approaches offer a growing and fundamental base of information, which when coupled with downstream functional genomics and proteomics can accelerate progress towards developing more efficient and sustainable control programs.     

Nematophagous fungi as a biological control agent for nematode parasites of small ruminants in Malaysia: a special emphasis on Duddingtonia flagrans

Approximately 2,800 fresh dung samples from animals, mainly ruminant livestock, were screened for the presence of nematophagous fungi in Malaysia. Arthrobotrys spp. was noted on numerous occasions, but only one isolate of Duddingtonia flagrans was made. For the purposes of producing sufficient quantities of this fungus for feeding trials in sheep, various, commonly available, cheap plant materials were tested as possible growth substrates. This showed that cereal grains (wheat, millet and rice) were the best media for fungal growth. Pen feeding trials were carried out using sheep, both naturally and experimentally infected with nematode parasites (predominantely Haemonchus contortus), to test the efficiency of D. flagrans when administered either in a grain supplement, or incorporated into a feed block. These showed that the fungus survived gut passage in sheep and that dose rates of approximately 1 x 10(6) D. flagrans spores / animal / day, reduced the percentage of infective larvae developing in faecal cultures by more than 90%. These results indicate that using D. flagrans as a biological control agent of nematode parasites, is a promising alternative to nematode parasite control of small ruminants in Malaysia, where anthelmintic resistance is now a major problem.     

Zoonotic implications of the swine-transmitted protozoal infections

Pig production is an important part of the economy in many countries. Domestic and wild pigs (Sus scrofa) are susceptible to a wide range of infectious and parasitic diseases. Some of these diseases are specifically limited to pigs while some of the other diseases are shared with other species of wildlife and domestic livestock. As the numbers and geographic distribution of wild and domestic swines continue to increase, it is certain that the number of contacts between these swines and domestic livestock will also increase, as will the probability of human exposure to the parasites of swine directly or indirectly. Here, we will discuss the protozoal infections of pigs, which have the potential to infect humans and provide reasonable risk assessment for zoonotic transmission.     

Plants as de-worming agents of livestock in the Nordic countries: historical perspective, popular beliefs and prospects for the future.

Preparations derived from plants were the original therapeutic interventions used by man to control diseases (including parasites), both within humans and livestock. Development of herbal products depended upon local botanical flora with the result that different remedies tended to develop in different parts of the world. Nevertheless, in some instances, the same or related plants were used over wide geographic regions, which also was the result of communication and/or the importation of plant material of high repute. Thus, the Nordic countries have an ancient, rich and diverse history of plant derived anthelmintic medications for human and animal use. Although some of the more commonly used herbal de-wormers were derived from imported plants, or their products, many are from endemic plants or those that thrive in the Scandinavian environment. With the advent of the modern chemotherapeutic era, and the discovery, development and marketing of a seemingly unlimited variety of highly efficacious, safe synthetic chemicals with very wide spectra of activities, herbal remedies virtually disappeared from the consciousness--at least in the Western world. This attitude is now rapidly changing. There is a widespread resurgence in natural product medication, driven by major threats posed by multi-resistant pest, or disease, organisms and the diminishing public perceptions that synthetic chemicals are the panacea to health and disease control. This review attempts to provide a comprehensive account of the depth of historical Nordic information available on herbal de-wormers, with emphasis on livestock and to provide some insights on potentially rewarding areas of "re-discovery" and scientific evaluation in this field.     

Developing vaccines to control protozoan parasites in ruminants: dead or alive?

Protozoan parasites are among some of the most successful organisms worldwide, being able to live and multiply within a very wide range of hosts. The diseases caused by these parasites cause significant production losses in the livestock sector involving reproductive failure, impaired weight gain, contaminated meat, reduced milk yields and in severe cases, loss of the animal. In addition, some protozoan parasites affecting livestock such as Toxoplasma gondii and Cryptosporidium parvum may also be transmitted to humans where they can cause serious disease. Data derived from experimental models of infection in ruminant species enables the study of the interactions between parasite and host. How the parasite initiates infection, becomes established and multiplies within the host and the critical pathways that may lead to a disease outcome are all important to enable the rational design of appropriate intervention strategies. Once the parasites invade the hosts they induce both innate and adaptive immune responses and the induction and function of these immune responses are critical in determining the outcome of the infection. Vaccines offer green solutions to control disease as they are sustainable, reducing reliance on pharmacological drugs and pesticides. The use of vaccines has multiple benefits such as improving animal health and welfare by controlling animal infections and infestations; improving public health by controlling zoonoses and food borne pathogens in animals; solving problems associated with resistance to acaricides, antibiotics and anthelmintics; keeping animals and the environment free of chemical residues and maintaining biodiversity. All of these attributes should lead to improved sustainability of animal production and economic benefit. Using different protozoan parasitic diseases as examples this paper will discuss various approaches used to develop vaccines to protect against disease in livestock and discuss the relative merits of using live versus killed vaccine preparations. A range of different vaccination targets and strategies will be discussed to help protect against: acute disease, congenital infection and abortion, persistence of zoonotic pathogens in tissues of food animals and passive transfer of immunity to neonates.